Coupling N–H Deprotonation, C–H Activation, and Oxidation: Metal-Free C(sp3)–H Aminations with Unprotected Anilines

An intramolecular oxidative C­(sp3)–H amination from unprotected anilines and C­(sp3)–H bonds readily occurs under mild conditions using t-BuOK, molecular oxygen and N,N-dimethylformamide (DMF). Success of this process, which requires mildly acidic N–H bonds and an activated C­(sp3)–H bond (BDE <...

Full description

Saved in:
Bibliographic Details
Published inJournal of the American Chemical Society Vol. 139; no. 45; pp. 16210 - 16221
Main Authors Evoniuk, Christopher J, Gomes, Gabriel dos Passos, Hill, Sean P, Fujita, Satoshi, Hanson, Kenneth, Alabugin, Igor V
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 15.11.2017
Amer Chemical Soc
Subjects
acidity
amination
aromatic compounds
carbon-hydrogen bond activation
chemical bonding
Chemistry
Chemistry, Multidisciplinary
dimethylformamide
heterocyclic nitrogen compounds
oxidants
oxidation
oxygen
Physical Sciences
Science & Technology
transition elements
AROMATIC-HYDROCARBONS
DENSITY FUNCTIONALS
CHEMICAL-SHIFTS NICS
RADICAL STABILITY
SOMO-HOMO CONVERSION
EFFICIENT SYNTHESIS
CONNECTOR GROUPS
SINGLET OXYGEN
SYNTHETIC APPROACH
INTRAMOLECULAR ADDITION
Online AccessGet full text

Cover

More Information
Summary:An intramolecular oxidative C­(sp3)–H amination from unprotected anilines and C­(sp3)–H bonds readily occurs under mild conditions using t-BuOK, molecular oxygen and N,N-dimethylformamide (DMF). Success of this process, which requires mildly acidic N–H bonds and an activated C­(sp3)–H bond (BDE < 85 kcal/mol), stems from synergy between basic, radical, and oxidizing species working together to promote a coordinated sequence of deprotonation: H atom transfer and oxidation that forges a new C–N bond. This process is applicable for the synthesis of a wide variety of N-heterocycles, ranging from small molecules to extended aromatics without the need for transition metals or strong oxidants. Computational results reveal the mechanistic details and energy landscape for the sequence of individual steps that comprise this reaction cascade. The importance of base in this process stems from the much greater acidity of transition state and product for the 2c,3e C–N bond formation relative to the reactant. In this scenario, selective deprotonation provides the driving force for the process.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0002-7863
1520-5126
1520-5126
DOI:10.1021/jacs.7b07519